Author:
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Fortner, Renée T.; Sarink, Danja; Schock, Helena; Johnson, Theron; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie-Christine; Boeing, Heiner; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Palli, Domenico; Sieri, Sabina; Mattiello, Amalia; Tumino, Rosario; Ricceri, Fulvio; Bueno de Mesquita, H. Bas; Peeters, Petra H. M.; van Gils, Carla H.; Weiderpass, Elisabete; Lund, Eiliv; Quirós, J. Ramón; Agudo, Antonio; Sánchez, María José; Chirlaque, María Dolores; Ardanaz, Eva; Dorronsoro, Miren; Key, Tim; Khaw, Kay-Tee; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A.; Riboli, Elio; Kaaks, Rudolf
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Abstract:
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Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER-, n = 386), matched 1: 1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: The associations between OPG and ER+ and ER-breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER-breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24-3.02]; p(trend) = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER-disease did not differ by menopausal status at blood collection (p(het) = 0.97), and we observed no heterogeneity by HT use at blood collection (p(het) >= 0.43) or age at breast cancer diagnosis (p(het) >= 0.30). Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER-breast cancer. |